Peroxynitrite is a known cytotoxic agent that plays a role in many pathological conditions. Various peroxynitrite decomposition catalysts and pathways are being explored to develop efficient therapeutic agents that can safely remove peroxynitrite from cells and tissues. Water-soluble porphyrins, such as iron(III) meso-tetra(2,4,6-trimethyl-3,5-disulfonato)porphine chloride (FeTMPS) and iron(III) meso-tetra(N-methyl4-pyridyl)porphine chloride (FeTMPyP), have been shown to react catalytically with peroxynitrite (ONOO-). However, their mechanisms are yet to be fully understood. In this study, we have explored the reactivity of FeTMPS in the catalytic decomposition of peroxynitrite. The mechanism of this complex process has been determined. According to this mechanism, Fe(III)TMPS is oxidized by peroxynitrite to produce oxoFe(lV)TMPS and NO2 (k1 = 1.3 x 10(5) M(-1)(s(-1). The porphyrin is then reduced back to Fe(III)TMPS by nitrite, but this rate (k2 = 1.4 x 10(4) M(-1)s(-1)) is not sufficient to maintain the catalytic process at the observed rate. The overall rate of peroxynitrite decomposition catalysis, kcat, was determined to be 6 x 10(4) M(-1)s(-1), under typical conditions. We have postulated that an additional reduction pathway must exist. Kinetic simulations showed that a reaction of oxoFe(IV)TMPS with NO2 (k3 = 1.7 x 10(7) M((-1)s(-1)) could explain the behavior of this system and account for the fast reduction of oxoFe(IV)TMPS to Fe(III). Using the kinetic simulation analysis, we have also shown that two other rearrangement reactions, involving FeTMPS and peroxynitrite, are plausible pathways for peroxynitrite decay. A "cage-return" reaction between the generated oxoFe(IV)TMPS and NO2 (k8 = 5.4 x 10(4) M(-1)s(-1)), affording Fe(III)TMPS and nitrate, and a reaction between oxoFe(IV)TMPS and peroxynitrite (k7 = 2.4 x 10(4) M(-1)s(-1)) that affords oxoFe(IV)TMPS and nitrate are presented. The mechanism of FeTMPS-catalyzed peroxynitrite decay differs markedly from that of FeTMPyP, providing some insight into the reactivity of metal centers with peroxynitrite and biologically important radicals such as NO2.